Treatment of rheumatoid arthritis with blackcurrant seed oil
BR. J. RHEUMATOL. (United Kingdom), 1994, 33/9 (847-852)
The objective of this study was to assess the clinical efficacy and side effects of blackcurrant seed oil (BCSO), in a randomized, double-blind, placebo controlled, 24-week trial in patients with RA and active synovitis. BCSO is rich in gammalinolenic acid (GLA) and alphalinoleinc acid (ALA). Both GLA and eicosapentaenoic acid which derives from ALA suppress inflammation and joint tissue injury in animal models. Treatment with BCSO resulted in reduction in signs and symptoms of disease activity in patients with RA (P < 0.05). In contrast, patients given a placebo showed no change in disease. Overall clinical responses (significant change in four measures) were no better in the treatment group than in the placebo group. No patients withdrew from BCSO treatment because of adverse reactions. However, many patients withdrew because BCSO and its placebo had to be administered in 15 large capsules daily. Nonetheless, the study indicates that BCSO is a potentially effective treatment for active RA. However, means must be found to reduce the size and number of capsules taken, so that larger studies of longer duration in RA patients can be undertaken.
Linolenic acid formulations for the treatment of premenstrual syndrome
CURR. OPIN. THER. PAT. (United Kingdom), 1992, 2/12 (2000-2002)
Novelty: A dietary treatment of the symptoms of pubertal premenstrual syndrome (PMS) is disclosed, comprising linolenic acids, calcium and iron sources, and optionally magnesium, vitamin B6 and other vitamins. The linolenic acids are thought to promote prostaglandin synthesis, hence alleviating PMS; the other constituents are present to replace excess losses during the pubertal period. Biology: A small clinical trial comprising pubescent females took an exemplified formulation of the claim daily for two months, and are stated to have shown improvements in daily energy, PMS symptoms and skin condition. However, no specific data are provided. Chemistry: Linolenic acid is provided as the native acid (Merck Index 5383) and/or as gamma-linolenic acid (Merck Index 5384) at about 0.1 mg/day in the form of Evening Primrose or Borage oils. Calcium is presented as the gluconate, carbonate or dicalcium phosphate; iron as ferrous sulphate, gluconate or fumarate. Example formulations are provided, incorporating the diverse constituents at their recommended daily intake levels or below.
The role of essential fatty acids and prostaglandins in the premenstrual syndrome
J. REPROD. MED. (USA), 1983, 28/7 (465-468)
Many of the features of the premenstrual syndrome are similar to the effects produced by the injection of prolactin. Some women with the premenstrual syndrome have elevated prolactin levels, but in most the prolactin concentrations are normal. It is possible that women with the syndrome are abnormally sensitive to normal amounts of prolactin. There is evidence that prostaglandin Esub 1, derived from dietary essential fatty acids, is able to attenuate the biologic actions of prolactin and that in the absence of prostaglandin Esub 1 prolactin has exaggerated effects. Attempts were made, therefore, to treat women who had the premenstrual syndrome with gamma-linolenic acid, an essential fatty acid precursor of prostaglandin Esub 1. Gamma-linolenic acid is found in human, but not cows', milk and in evening primrose oil, the preparation used in these studies. Three double-blind, placebo-controlled studies, one large open study on women who had failed other kinds of therapy for the premenstrual syndrome and one large open study on new patients all demonstrated that evening primrose oil is a highly effective treatment for the depression and irritability, the breast pain and tenderness, and the fluid retention associated with the premenstrual syndrome. Nutrients known to increase the conversion of essential fatty acids to prostaglandin Esub 1 include magnesium, pyridoxine, zinc, niacin and ascorbic acid. The clinical success obtained with some of these nutrients may in part relate to their effects on essential fatty acid metabolism.
Effects of dietary supplementation with arachidonic acid rich oils on nerve conduction and blood flow in streptozotocin-diabetic rats
Prostaglandins Leukotrienes and Essential Fatty Acids (United Kingdom), 1997, 56/5 (337-343)
Diabetes mellitus is associated with defective essential fatty acid desaturation. In experimental models this contributes to characteristic reductions in peripheral nerve conduction velocity (NCV) and blood flow, which may be corrected by dietary supplementation with gamma-linolenic acid (GLA) rich oils to bypass the Delta-6 desaturation deficit. There is debate about the mechanism of this improvement, including whether it depends on synthesis of series 1 prostanoids derived from di-homo GLA or series 2 prostanoids from arachidonic acid (ARA). The aim was to assess the efficacy of two ARA-rich (similar 39% content) oils in correcting neurovascular dysfunction in streptozotocin-induced diabetic rats. After 6 weeks of untreated diabetes, rats were treated for a further 2 weeks with 1% dietary oil supplements before assessment of sciatic motor NCV and endoneurial blood flow. NCV was 19% reduced in diabetic rats and this was largely (similar 86%) corrected by both oil treatments. A 48% deficit in endoneurial nutritive blood flow with diabetes was similar 70% reversed by the two oils, vascular conductance being in the non-diabetic range. Thus, nerve conduction and perfusion deficits in diabetic rats are corrected by ARA-rich oil treatment. The magnitudes of these changes were similar to expectations based on previous studies of GLA-rich oils, therefore it is likely that the neurovascular effect of increased synthesis of series 2 prostanoids makes a major contribution to the beneficial action of n-6 essential fatty acids in experimental diabetic neuropathy.
Interaction between oxidative stress and gamma-linolenic acid in impaired neurovascular function of diabetic rats
American Journal of Physiology - Endocrinology and Metabolism (USA), 1996, 271/3 34-3 (E471-E476)
Nerve conduction and perfusion deficits in diabetic rats depend on increased oxidative stress and impaired n-6 essential fatty acid metabolism, which are corrected by free radical scavenger and gamma-linolenic acid (GLA)- rich oil treatments, respectively. We investigated the interaction between these mechanisms on conduction velocity and endoneurial blood flow by use of low-dose antioxidant (BM15.0639) and GLA treatments, alone and in combination. After 8 wk of streptozotocin-induced diabetes, sciatic motor conduction velocity was 20.9% reduced. Treatment with GLA or BM15.0639 for the final 2 wk corrected this deficit by 18.5 and 20.0%, respectively; however, joint treatment caused 71.5% improvement, corresponding to a 7.5- fold amplification of individual drug effects. A 48.3% deficit in sciatic nutritive endoneurial blood flow was corrected by 34.8 and 24.8% with GLA and BM15.0639 treatments, respectively. With joint treatment, the flow improvement of 72.5% was greater than expected from individual drug effects, indicating a facilitatory interaction. Thus the synergistic effect of combined antioxidant and n-6 essential fatty acid treatment could potentially provide increased therapeutic power against diabetic neuropathy.
Comparison of the effects of ascorbyl gamma-linolenic acid and gamma-linolenic acid in the correction of neurovascular deficits in diabetic rats
Diabetologia (Germany), 1996, 39/9 (1047-1054)
Essential fatty acid metabolism is impaired by diabetes mellitus and gamma-linolenic acid rich treatments such as evening primrose oil correct deficits in nerve conduction and endoneurial blood flow in diabetic rats. Other mechanistically unrelated treatments, such as antioxidants and aldose reductase inhibitors have a similar effect and there may be positive interactions with multiple treatments. Our aim was to compare the efficacy of a novel essential fatty acid derivative, ascorbyl gamma-linolenic acid, with that of gamma-linolenic acid in correcting diabetic neurovascuIar deficits. Eight weeks of diabetes caused 20.4 and 48.2 % reductions in sciatic motor conduction velocity and nutritive endoneurial blood flow, respectively. Treatment was given for the last 2 weeks with gamma-linolenic acid (100 mg.kg-1 day-1) either in pure form or as ascorbyl gamma-linolenic acid, an equivalent dose of ascorbate (21 mg.kg-1 day) or jointly with ascorbate and gamma-linolenic acid. Conduction velocity was corrected by 39.8, 87.4, 13.2 and 66.8 % with gamma-linolenic acid, ascorbyl gamma-linolenic acid, ascorbate and gamma-linolenic acid plus ascorbate, respectively. Corresponding ameliorations of the nutritive blood flow deficit were 44.0, 87.4, 13.2 and 65.7 %. For the gamma-linolenic acid plus ascorbate combination, and especially for ascorbyl gamma-linolenic acid, the magnitude of correction for conduction velocity and blood flow was greater than expected for simple addition of ascorbate and gamma-linolenic acid, indicating a synergistic interaction. Thus, with an efficacy 40 times that of evening primrose oil in rats, ascorbyl gamma-linolenic acid may be a suitable candidate for clinical trials of diabetic neuropathy.
Comparison of the effects of evening primrose oil and triglycerides containing gamma-linolenic acid on nerve conduction and blood flow in diabetic rats.
J Pharmacol Exp Ther (UNITED STATES) Apr 1995
The aim was to ascertain whether the ability of evening primrose oil (EPO) treatment to correct peripheral nerve dysfunction in streptozotocin-diabetic rats depends on a gamma-linolenic acid (GLA)-containing triglyceride constituent, di-linolein mono-gamma-linolenat e (DLMG). A second objective was to investigate whether the triglyceride conformation of GLA affects efficacy, using tri-gamma-linolenate (TGLA), which is not present in EPO. Third, we examined the actions of these omega-6 essential fatty acid-containing oils on sciatic nerve blood flow to establish a common mechanism. After 6 weeks of diabetes, sciatic motor nerve conduction velocity (NCV) was 21% reduced. EPO treatment caused dose-dependent increases in NCV that reached asymptote within 7 days. DLMG and TGLA, at doses matched for GLA content, had effects indistinguishable from those of EPO. Sciatic blood flow, 47.2% reduced by diabetes, was partially normalized by EPO, DLMG and TGLA. In contrast, sunflower oil (which does not contain GLA) did not alter NCV or blood flow. The data therefore provide strong evidence that DLMG is the active component of EPO and suggest that correction of nerve dysfunction involves a vascular action. The precise triglyceride configuration of GLA does not appear crucial to its effects in experimental diabetic neuropathy.
The effects of gamma-linolenic acid on breast pain and diabetic neuropathy: possible non-eicosanoid mechanisms.
Prostaglandins Leukot Essent Fatty Acids (SCOTLAND) Jan 1993
Gamma-linolenic acid (GLA) has recently been found to be beneficial in the management of breast pain and of diabetic neuropathy. GLA is a precursor of unsaturated fatty acids which are important in membrane structures, as second messengers in their own right and as precursors of eicosanoids. While the mechanisms of GLA action are likely to be complex, non-eicosanoid effects are probably of substantial importance. These effects include modification of membrane fluidity and of the functions of lipid-associated receptors and changes in the inositol cycle.
The use of gamma-linolenic acid in diabetic neuropathy.
Agents Actions Suppl (SWITZERLAND) 1992, 37 p120-44
EF4 is an entirely new approach to the management of diabetic neuropathy. EF4 (providing gamma-linolenic acid or gamolenic acid, GLA) has been shown to reverse existing diabetic neuropathy in trials in seven centres. Diabetic animals and humans have a reduced ability to convert dietary linoleic acid to GLA. GLA and its metabolites are required for normal neuronal structure and function and a normal microcirculation. The lack of GLA and its metabolites may play a major role in the development of the neuropathy. EF4 helps to correct the biochemical defects, restores levels of GLA metabolites towards normal and produces highly significant clinical and neurophysiological improvements in diabetic neuropathy.
Treatment of diabetic neuropathy with gamma-linolenic acid
DIABETES CARE (USA), 1993, 16/1 (8-15)
OBJECTIVE - To compare the effects of placebo and GLA on the course of mild diabetic neuropathy over 1 yr. RESEARCH DESIGN AND METHODS - We entered 111 patients with mild diabetic neuropathy from seven centers into a randomized, double-blind, placebo-controlled parallel study of GLA at a dose of 480 mg/day. MNCV, SNAP, CMAP, hot and cold thresholds, sensation, tendon reflexes, and muscle strength were assessed by standard tests in upper and lower limbs. RESULTS - For all 16 parameters, the change over 1 yr in response to GLA was more favorable than the change with placebo, and for 13 parameters, the difference was statistically significant. Sex, age, and type of diabetes did not influence the result, but treatment was more effective in relatively well-controlled than in poorly-controlled diabetic patients. CONCLUSIONS - GLA had a beneficial effect on the course of diabetic neuropathy.
Feeding conjugated linoleic acid to animals partially overcomes catabolic responses due to endotoxin injection.
Biochem Biophys Res Commun (UNITED STATES) Feb 15 1994, 198 (3 p1107-12)
The ability of conjugated linoleic acid to prevent endotoxin-induced growth suppression was examined. Mice fed a basal diet or diet with 0.5% fish oil lost twice as much body weight after endotoxin injection than mice fed conjugated linoleic acid. By 72 hours post injection, mice fed conjugated linoleic acid had body weights similar to vehicle injected controls; however, body weights of basal and fish oil fed mice injected with endotoxin were reduced. Conjugated linoleic acid prevented anorexia from endotoxin injection. Splenocyte blastogenesis was increased by conjugated linoleic acid.
Lipids and neurological diseases
MED. HYPOTHESES (United Kingdom), 1991, 34/3 (272-274)
Neurological diseases, such as multiple sclerosis (MS), Sjogren-Larsson syndrome, Reye's syndrome, and Refsum's syndrome (herediopathica atactica polyneuroformis), and many others afflict millions of persons yearly and have no successful treatment available. A common aspect of these diseases appears to be a lipid imbalance involving the essential fatty acids (EFA), linoleic and linolenic, and trace fatty acids which result from faulty lipid metabolism. It is proposed that treatments for these diseases should be sought through diet and metabolic enzymes rather than drugs.
Relevance of essential fatty acids in medicine and nutrition
AKTUEL. ENDOKRINOL. STOFFWECHSEL (GERMANY, WEST), 1986, 7/1 (18-27)
The polyunsaturated fatty acids linoleic and alpha-linolenic acid are essential dietary constituents in human nutrition. Their biological effects are based on their structural function in membranes and their role as precursors of prostaglandins, thromboxanes and leukotrienes. An insufficient supply leads to a deficiency syndrome with skin lesions, reduced food utilization, disturbed functions of the nervous system and other organs and an altered fatty acid pattern of plasma lipids. Patients at an increased risk are infants due to their high requirements and marginal body stores, and patients with an inadequate supply because of fat malabsorption or malnutrition. A deficiency syndrome can develop very quickly under fat-free parenteral nutrition. Disturbances in fatty acid metabolism are observed in diabetes mellitus, multiple sclerosis, atopic eczema and a number of hereditary diseases. The essential fatty acid content of the diet influences reactions of the immune system, especially the cellular immunity. The development of cardiovascular lesions and their complications is modulated by the dietary supply of essential fatty acids. Long chain, highly polyunsaturated omega3-fatty acids found in marine fish may have particular potent antiatherosclerotic effects.
Essential fatty acids in perspective
HUM. NUTR. CLIN. NUTR. (ENGLAND), 1984, 38/4 (245-260)
1. There are two families of essential fatty acids, the linoleic and linolenic. Linoleic acid (C18:2n-6), found mainly in vegetative seed oils, is desaturated and elongated in the body, forming arachidonic acid (C20:4n-6). Linolenic acid (C18:3n-3), the main dietary source of which is leaves, is desaturated and elongated, forming two fatty acids that are prevalent in fish oils: timnodonic (C20:5n-3) and clupanodonic (C22:6n-3). EFA are very easily peroxidized in air, but vitamin E protects against this. 2. There are three functions of EFA. The most important is as part of phospholipids in all animal cellular membranes: in deficiency of EFA faulty membranes are formed. A second is in the transport and oxidation of cholesterol: EFA tend to lower plasma cholesterol. A third function is as precursors of prostanoids which are only formed from EFA. 3. Deficiency of EFA in experimental animals causes lesions mainly attributable to faulty cellular membranes: sudden failure of growth, lesions of skin and kidney and connective tissue, erythrocyte fragility, impaired fertility, uncoupling of oxidation and phosphorylation. 4. In man pure deficiency of EFA has been studied particularly in persons fed intravenously. A relative deficiency (that is, a low ratio in the body of EFA to long-chain saturated fatty acids and isomers of EFA) is common on Western diets and plays an important part in the causation of atherosclerosis, coronary thrombosis, multiple sclerosis, the triopathy of diabetes mellitus, hypertension and certain forms of malignant disease. 5. Various factors affect the dietary requirements of EFA.
Polyunsaturated (essential) fatty acids and their importance in pathogenesis, diagnosis and therapy of multiple sclerosis
FORSTSCHR. NEUROL. PSYCHIATR. (GERMANY, WEST), 1982, 50/6 (173-189)
Various aspects concerning the pathogenetic involvement of polysaturated (essential) fatty acids as biochemical co-factors in developing multiple sclerosis (MS) are reported in great detail. Our own studies have also confirmed that differences in the intake or utilization of essential fatty acids do not biochemically induce significant changes in myelin, serum or blood cells. This has long been suspected. The concept of nutritionally or metabolically induced generalized defects in all membranes, especially in the myelin sheath, as a predisposing factor to an increased susceptibility for the development of MS, provoked a gamut of pertinent studies frequently producing controversial results. Hence, these conceptions concerning the pathogenetic involvement of essential fatty acids in MS have been put to rest - even more so after the role of prostaglandins in immunoregulation had become more apparent, whose biological precursors are essential fatty acids. Thus, the immunosuppressive effect of high dosage of essential fatty acids under experimental conditions could be explained, disclosing new assessments concerning therapy, new pathogenetic models and further biochemical research. (180 references.)
Supplementation of polyunsaturated fatty acids in multiple sclerosis.
Ital J Neurol Sci (ITALY) Jun 1992, 13 (5) p401-7
For several years polyunsaturated fatty acids (PUFAs) and in particular essential fatty acids (EFAs) have been proposed for the treatment of multiple sclerosis (MS). There are contrasting data in literature regarding the effects of the n-6 and the n-3 PUFA series on different aspects of the disease, in particular on the frequency and severity of relapses and platelet function. This can be ascribed to the different criteria of patient selection in relation to the form and severity of disease at the beginning of the various studies. Till now authors have tended to consider the effect of PUFA supplementation only on some clinical aspects of the disease. Modification in the more sensitive indices (immunological or biochemical) of the disease activity should be taken into account and also the influence of dietary lipid intake by patients in relation to n-3 or n-6 EFA supplementation. (50 Refs.)
Essential fatty acid and lipid profiles in plasma and erythrocytes in patients with multiple sclerosis.
Am J Clin Nutr (UNITED STATES) Oct 1989, 50 (4) p801-6
This study was conducted to investigate the possible differences in erythrocyte lipid composition, which might account for the previously reported increase in erythrocyte membrane zinc levels in patients with multiple sclerosis (MS). Compared with healthy control subjects, plasma lipids in patients with MS contained less sphingomyelin but more phosphatidylserine and the cholesterol-phospholipid ratio was 42% higher in the plasma from MS patients (p less than 0.01). In erythrocytes from MS patients, phosphatidylinositol was lower and erythrocyte cholesterol per milligram protein was significantly lower than concentrations in healthy control subjects (p less than 0.01). Among the long-chain fatty acids, the omega-3 fatty acids were lower in plasma from MS patients and linoleic acid was lower in erythrocyte ghosts from MS patients (p less than 0.01). We conclude that altered levels of cholesterol in plasma and erythrocytes from MS patients may contribute to increased erythrocyte-membrane Zn in MS patients. It cannot be stated with certainty whether the altered fatty acid profiles in MS patients were a function of the disease or of altered fatty acid intake.
Polyunsaturated fatty acids in treatment of acute remitting multiple sclerosis.
Br Med J (ENGLAND) Nov 18 1978, 2 (6149) p1390-1
One hundred and sixteen patients with acute remitting multiple sclerosis (MS) took part in a double-blind controlled trial of treatment with polyunsaturated fatty acids and were randomly allocated to one of four groups. Two groups received linoleic acid, one alone as a spread and one with gamma-linolenic acid in capsules (Naudicelle); and two control groups received oleic acid, one as a spread and one in capsules. Rates of clinical deterioration and frequencies of attacks were not significantly different between treated and control groups. Exacerbations were shorter and less severe in patients receiving a high dose of linoleic acid than in controls, but those receiving a lower dose--that is, Naudicelle--showed no such difference. Thus supplementing the diet with 20 g linoleic acid marginally affected the duration and severity of relapses of MS but had no effect on overall disability. The dose of Naudicelle used provided insufficient supplementation.
The effect of gamma-linolenic acid on clinical status, red cell fatty acid composition and membrane microviscosity in infants with atopic dermatitis.
SO:Drugs Exp Clin Res. 1994. 20(2). P 77-84
A double blind placebo-controlled study of two doses of gamma-linolenic acid, provided by evening primrose oil (EPO, Epogam, Searle, U.K.), in children with atopic dermatitis was performed: 1) to examine the effect of gamma-linolenic acid administration on the clinical status of children with atopic dermatitis and abnormalities of IgE-mediated immune responses compared to those without such IgE abnormalities; 2) to investigate the effect of gamma-linolenic acid on red cell fatty acid composition and 3) to assess whether treatment with gamma-linolenic acid induced changes in red cell membrane microviscosity. A significant improvement in the overall severity of the clinical condition was seen in children treated with gamma-linolenic acid, independent of whether the children had manifestations of IgE-mediated allergy. Furthermore, gamma-linolenic acid treatment increased the percentage content of n-6 fatty acids in erythrocyte cell membrane; this increase was more marked in the membranes of children treated with high doses of EPO. In the high dose group a significant increase in dihomogamma-linolenic acid (DGLA) occurred. This may be of particular relevance because of the potential importance of DGLA as a precursor of antiinflammatory prostanoids. Red cell membrane microviscosity did not change in any group after treatment with EPO, even in high doses, despite a significant increase in the proportion of long chain polyunsaturated fatty acids.
Fatty acid compositions of plasma lipids in atopic dermatitis/asthma patients.
Arerugi. 1994 Jan. 43(1). P 37-43
The proportions of linoleic acid in total plasma lipids and phospholipids were significantly greater and those of oleic acid were lower in pre-puberal and puberal atopic patients as compared with age-matched healthy controls. The n-3/n-6 fatty acid ratio of the triacylglycerol fraction was also lower in atopic patients. However, no significant decreases in the proportions of dihomo-gamma-linolenic acid and arachidonic acid were observed in plasma lipids of atopic patients, suggesting that delta 6-desaturase activity is not impaired in atopic patients. We provide an explanation for the beneficial effects of raising the n-3/n-6 ratio of dietary oils in the context of suppressing allergic hyper-reactivity in humans.
Gamma-linolenic acid for attention-deficit hyperactivity disorder: placebo-controlled comparison to D-amphetamine.
Biol Psychiatry (UNITED STATES) Jan 15 1989, 25 (2) p222-8
In a Latin-square double-crossover with random assignment to sequence, 18 boys, aged 6-12 years, with attention-deficit hyperactivity disorder received 1 month each of placebo, D-amphetamine, and Efamol (evening primrose oil containing gamma-linolenic acid, with vitamin E as preservative). Parents' ratings were noncontributory. Teachers' ratings showed a trend of Efamol effect between placebo and D-amphetamine. The trend reached significance (p less than 0.05) only on Conners Hyperactivity Factor. Dosage may be crucial; 8 Efamol capsules per day were used in this study. Heuristic data scrutiny suggested possible interaction (sequence effect). Further study with a different design and dose is suggested. This study does not establish Efamol as an effective treatment.
Metabolism of linoleic and alpha-linolenic acids in cultured cardiomyocytes: Effect of different n-6 and n-3 fatty acid supplementation
Molecular and Cellular Biochemistry (USA), 1996, 157/1-2 (217-222)
The metabolites of linoleic (LA) and a-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% of 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.
Essential fatty acid metabolism in patients with essential hypertension, diabetes mellitus and coronary heart disease.
Prostaglandins Leukot Essent Fatty Acids (SCOTLAND) Jun 1995, 52 (6) p387-91
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, alpha-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 E1, (PGE1), prostacyclin (PGI2), and PGI3, 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.( ABSTRACT TRUNCATED AT 250 WORDS)
The effect of unsaturated fatty acids on membrane composition and signal transduction in HT-29 human colon cancer cells
Cancer Letters (Ireland), 1996, 108/1 (25-33)
The objective of the present study was to investigate the effect of membrane fatty acid (FA) composition on the activity of phospholipase C (PLC) in HT-29 human colon cancer cells. The membrane FA composition was altered by supplementing cultured cells with FAs of different composition. The FAs were stearic acid (18:0;SA), gammalinolenic acid (18:3omega6;gammaLnA); a linolenic acid (18:3omega3; alphaLnA;); eicosapentaenoic acid (20:5omega3;EPA) and docosahexaenoic acid (22:6omega3;DHA). The fatty acids were supplemented as a FA/BSA complex. Cells supplemented with SA served as the control. Tumor growth was followed by counting the number of cells in culture. The results indicate that polyunsaturated fatty acid (PUFA) supplementation had no consistent effect on tumor growth from 1 day to another throughout the 15 days of growth. The fatty acid composition of membranes indicates that cells incorporated and modified the supplemented fatty acids by desaturation, elongation and retroconversion. The unsaturation index (UI) of membranes of cells supplemented with EPA and DHA was higher than other groups. PLC activity; measured in the absence of GTPgamma(S) in the assay mixture; was not influenced by membrane FA modification. However, in the presence of GTPgamma(S) PLC of cells supplemented with 18:3(omega6) was the lowest among the groups. It has been shown that 18:3(omega6) accumulated the most in the phosphatidylethanolamine (PE) fraction. There was a negative correlation between the activity of PLC in the presence of G protein activation and PE 18:3(omega6) content without affecting UI. It was concluded that G protein may be sensitive to the level of 18:3(omega6) content and not to the general fluidity of the membranes.
Suppression of nitric oxide production in lipopolysaccharide-stimulated macrophage cells by omega3 polyunsaturated fatty acids
Japanese Journal of Cancer Research (Japan), 1997, 88/3 (234-237)
Although nitric oxide (NO) is an important biological mediator, its excessive production in inflammation is thought to be a causative factor for cellular injury and, over the long term, cancer. In the present study, the effects of several fatty acids on NO production in murine macrophage cell line RAW264 cells stimulated with lipopolysaccharide were examined. Suppression of NO production was observed with the omega3 polyunsaturated fatty acids (PUFAs), docosahexaenoic acid, eicosapentaenoic acid and alpha-linolenic acid, in a dose-dependent fashion. In contrast, no inhibition was observed with omega6 PUFA (linoleic acid), omega9 PUFA (oleic acid) or a saturated fatty acid (stearic acid). Western and northern blot analyses suggested that suppression of the induction of inducible NO synthase gene expression is responsible for the inhibition of NO production by omega3 PUFAs. The inhibitory effect of omega3 PUFA on NO production in activated macrophages could contribute to their cancer chemopreventive influence.
Multiple sclerosis: effect of gamma linolenate administration upon membranes and the need for extended clinical trials of unsaturated fatty acids.
Eur Neurol (SWITZERLAND) 1983, 22 (1) p78-83
Electrophoretic mobility studies of red blood cells from subjects with multiple sclerosis indicate that treatment with unsaturated fatty acids must continue for at least 2 years before normal reactivity is restored by currently available tests. If this applies to myelin also, then clinical trials aimed at treating the recognized multiple sclerosis subject by polyunsaturated fatty acids really begin after 2 years, and this should be recognized when a trial program is drawn up.
Effect of prolonged ingestion of gamma-linolenate by MS patients.
Eur Neurol (SWITZERLAND) 1978, 17 (2) p67-76
The absolute electrophoretic mobility of erythrocytes from MS patients is reduced in the presence of 0.08 mg/ml of linoleic or arachidonic acid, whilst that of normal or other neurological disease patients is increased in the presence of these acids. When an MS patient ingests gamma-linolenate (in capsule form equivalent to 413.4 mg of gamma-linolenic acid and 2.664 g of linoleic acid per day) the reaction of MS erythrocytes begins to change. After 3 or 4 months the reaction becomes normal with arachidonic acid (i.e. mobility is speeded up) and 2 months or so later this occurs also with linoleic acid. Very prolonged administration of gamma-linolenate leads to a markedly increased sensitivity to the effect of prostaglandins (PGE2) on RBC mobility. The observations are interpreted to mean the induction of a biochemical-biophysical change in the membranes, and the significance of this in the aetiology and treatment of multiple sclerosis is discussed.
Treatment of rheumatoid arthritis with blackcurrant seed oil
re of evening primrose oil and fish oil containing Gamma-linolenic acid (GLA), Eicosapentaenoic acid (EPA), and Docosahexaenoic acid (DHA) had a significantly lower incidence of edema (13%, p = 0.004). The group receiving Magnesium Oxide had statistically significant fewer subjects who developed hypertension of pregnancy. There were 3 cases of eclampsia, all in the Placebo group.