gamma-linolenic-acid and Alcoholism

Essential fatty acids (EFAs) are major structural components of the brain and through their effects on membrane properties can influence nerve conduction, transmitter release, and transmitter action. Prostaglandins (PGs) derived from EFAs have profound behavioral effects and are also able to modify conduction and transmitter function. Effects of alcohol on EFAs and PGs are therefore good candidates for explaining at least some of the actions of alcohol on brain function. Ethanol has three main known actions on EFA and PG metabolism: it reduces blood linoleic acid levels and induces or exaggerates EFA deficiency states; it blocks metabolism of linoleic acid to EFA metabolites which are known to be important in brain structure; and it enhances conversion of the linoleic acid metabolite, dihomo-gamma-linolenic acid, to PGE1. This review demonstrates that some of the short-term behavioral effects of ethanol and some of its long-term adverse effects on brain, liver, and other tissues may be partly explicable in terms of ethanol actions on EFA and PG metabolism. Modification of such metabolism by dietary and other means has already been shown to influence the effects of alcohol and alcohol withdrawal in both humans and animals. This promises to be a fruitful source of investigation with substantial implications for the understanding and treatment of alcoholism.

Topics: Alcoholism; Alprostadil; Animals; Drug Interactions; Ethanol; Fatty Acids, Essential; Fatty Acids, Unsaturated; Fatty Liver, Alcoholic; Female; gamma-Linolenic Acid; Guinea Pigs; Humans; Linoleic Acid; Linoleic Acids; Linolenic Acids; Lithium; Male; Mice; Oenothera biennis; Plant Oils; Prostaglandins; Rats; Research; Substance Withdrawal Syndrome

Evidence for the role of essential fatty acids in alcohol dependence is reviewed. If alcohol-induced tissue damage is associated with impaired fatty acid and phospholipid metabolism, supplements of essential fatty acids might be beneficial in the treatment of alcoholics. The evidence for this effect is examined.

Topics: Adult; Age Factors; Alcoholism; Brain; Clinical Trials as Topic; Cognition; Diazepam; Double-Blind Method; Erythrocyte Membrane; Ethanol; Fatty Acids, Essential; Fatty Acids, Unsaturated; gamma-Linolenic Acid; Humans; Linoleic Acids; Liver Cirrhosis, Alcoholic; Magnetic Resonance Spectroscopy; Middle Aged; Oenothera biennis; Phospholipids; Plant Oils; Substance Withdrawal Syndrome

The aim of this study was to determine the activity of the lysosomal exoglycosidases: alpha-mannosidase (MAN), alpha-fucosidase (FUC), and beta-glucuronidase (GLUCUR) in serum of alcohol-dependent men supplemented and not supplemented with borage oil enriched with vitamin E. Serum was collected from eight social drinkers and 16 alcohol-dependent men after a drinking period. The activity of exoglycosidases and the concentration of protein in serum were determined. The increase in specific activity of MAN and GLUCUR was significant in serum of alcohol-dependent men both not supplemented and supplemented with borage oil enriched with vitamin E, in comparison with the specific activity in serum of social drinkers. In serum of alcohol-dependent men treated with borage oil enriched with vitamin E, specific activity of MAN and GLUCUR fluctuated in comparison with alcohol-dependent men not supplemented. Specific activity of FUC in serum of alcohol-dependent men both not supplemented and supplemented with borage oil enriched with vitamin E showed a tendency to increase, in comparison with social drinkers. Specific activity of FUC had a tendency to decrease in serum of alcohol-dependent men supplemented with borage oil enriched with vitamin E, in comparison with alcohol-dependent men not supplemented. Thus, supplementation of alcohol-dependent men after a long-lasting drinking period with borage oil and vitamin E did not change the rate of catabolism of the oligosaccharide chains of glycoconjugates, as evaluated by serum activity of exoglycosidases.

Topics: Alcoholism; Borago; Dietary Supplements; gamma-Linolenic Acid; Glycoside Hydrolases; Humans; Lysosomes; Male; Plant Oils; Vitamin E

Evidence for the role of essential fatty acids in alcohol dependence is reviewed. If alcohol-induced tissue damage is associated with impaired fatty acid and phospholipid metabolism, supplements of essential fatty acids might be beneficial in the treatment of alcoholics. The evidence for this effect is examined.

Topics: Adult; Age Factors; Alcoholism; Brain; Clinical Trials as Topic; Cognition; Diazepam; Double-Blind Method; Erythrocyte Membrane; Ethanol; Fatty Acids, Essential; Fatty Acids, Unsaturated; gamma-Linolenic Acid; Humans; Linoleic Acids; Liver Cirrhosis, Alcoholic; Magnetic Resonance Spectroscopy; Middle Aged; Oenothera biennis; Phospholipids; Plant Oils; Substance Withdrawal Syndrome

This study investigates the effects of n-6 polyunsaturated fatty acids (PUFAs), in the form of dietary Evening Primrose Oil (EPO) and safflower oil, on the development of tolerance to ethanol. The degree of fluorescence polarization of the fluoroprobes DPH, PROP-DPH, and TMA-DPH in isolated cortical synaptosomal membranes was measured. In addition, the development of tolerance, as shown by changes in synaptosomal membrane fluidity after an acute in vitro ethanol challenge, was also determined after 20 weeks of ethanol administration, either alone or together with a PUFA-enriched diet. Although the administration of EPO-enriched diet did not significantly render the inner core of the cortical synaptosomal membrane tolerant to the acute ethanol challenge, concomitant administration of ethanol and EPO was found to increase further the rigidity and tolerance to the acute ethanol challenge in the inner core. Chronic administration of safflower oil, which lacks gamma-linolenic acid (18:3, n-6) but like EPO contains linoleic acid, either alone or together with chronic ethanol had no effect on synaptosomal membrane fluidity after an acute ethanol challenge. The results suggest that gamma-linolenic acid or its metabolites may have an important role to play in the development of tolerance to chronic ethanol.

Topics: Alcoholism; Animals; Brain; Dietary Fats, Unsaturated; Drug Tolerance; Fatty Acids, Essential; gamma-Linolenic Acid; Linoleic Acids; Male; Membrane Fluidity; Oenothera biennis; Plant Oils; Rats; Rats, Sprague-Dawley; Safflower Oil; Synaptosomes

Chronic ethanol administration significantly decreased the percentage of arachidonate and significantly increased the linoleate: arachidonate ratio in the cortical synaptosomal phosphatidylinositol (PI) of rats. However, concomitant administration of evening primrose oil (rich in gamma-linolenic acid) reversed the effects seen with ethanol alone. These results suggest that the decrease of arachidonate, especially in PI, caused by chronic administration of ethanol may be overcome by systemic administration of gamma-linolenic acid.

Topics: Alcoholism; Animals; Arachidonic Acid; Cerebral Cortex; Fatty Acids; gamma-Linolenic Acid; Linoleic Acid; Linoleic Acids; Linolenic Acids; Male; Phosphatidylcholines; Phosphatidylethanolamines; Phosphatidylinositols; Phosphatidylserines; Rats; Rats, Inbred Strains; Synaptosomes

Chronic ethanol administration to adult rats results in an increase in the linolenic (18:2) to arachidonic (20:4) acid ratios in brain phospholipids. Administration of a diet rich in essential fatty acids can reverse some of the effects of chronic ethanol administration on neuronal membranes. In this study we investigated the effect of ethanol on the neuronal membranes of rat pups and also the effect of the concomitant administration of gamma linolenic acid (18:3) as a component of Evening Primrose Oil (EPO). We found an increase in the concentration of several saturated fatty acids that are components of the phospholipids and a decrease in the mono- and polyunsaturated fatty acid content. EPO was found to attenuate the effect of ethanol in inhibiting the synthesis of polyunsaturated fatty acids. These effects of EPO are probably a direct consequence of the essential fatty acids in the oil circumventing the inhibitory effects of ethanol on polyunsaturated fatty acid synthesis.

Topics: Alcoholism; Animals; Animals, Newborn; Brain; Dose-Response Relationship, Drug; Ethanol; Fatty Acids; Female; gamma-Linolenic Acid; Linolenic Acids; Phospholipids; Pregnancy; Rats; Rats, Wistar

In the context of recent work showing numerous interactions between ethanol, essential fatty acids (EFA) and prostanoids, we have evaluated the effects of gamma-linolenic acid methyl ester (GLA 99%; 18:3, n-6), on hepatic pathology induced by ethanol in rats. Groups of animals were pair-fed an alcohol-containing liquid diet or an iso-caloric maltose-dextrin diet. Animals fed ethanol for ten days had markedly increased hepatic triglycerides and histological evidence of fatty liver. These effects were partially attenuated by administration of GLA during the period of ethanol administration.

Topics: Alcoholism; Animals; Disease Models, Animal; Fatty Liver, Alcoholic; gamma-Linolenic Acid; Humans; Linolenic Acids; Liver; Male; Rats; Rats, Inbred Strains; Triglycerides

Prostaglandin E1 (PGE1) and prostanoid precursor fatty acids enhance the acute sedative effects of ethanol in mice, and reduce the intensity of withdrawal after chronic exposure to ethanol. Aspirin, and other inhibitors of prostanoid synthesis, attenuate ethanol's sedative effects, and interfere with the beneficial effects of prostanoid precursors (but not of PGE1 itself) in withdrawal. Neither aspirin nor indomethacin administered alone affect withdrawal behavior. In contrast, ethanol impairment of rotorod behavior is not affected by prostanoid precursors nor by aspirin. These findings support a role for prostanoids as modulators (? mediators) of certain direct effects of ethanol and a role for prostanoid deficiency in the pathogenesis of withdrawal behavior.

Topics: Alcoholism; Alprostadil; Animals; Aspirin; Brain; Ethanol; Fatty Acids; Fatty Acids, Essential; Fatty Acids, Unsaturated; gamma-Linolenic Acid; Humans; Ibuprofen; Indomethacin; Linoleic Acids; Linolenic Acids; Male; Mice; Oenothera biennis; Plant Oils; Prostaglandins; Prostaglandins E; Prostanoic Acids; Substance Withdrawal Syndrome

Topics: Alcoholism; Animals; Carnitine; Ethanol; Fatty Acids, Unsaturated; gamma-Linolenic Acid; Humans; Linolenic Acids; Rats; Thiamine

Alcohol has at least two actions on essential fatty acid (EFA) and Prostaglandin (PG) metabolism. It enhances the conversion of dihomogammalinolenic acid (DGLA) to PGE1 but it blocks the activity of the delta-6-desaturase, an enzyme necessary for replenishment of DGLA stores from dietary precursors. The acute effect of ethanol is therefore an increased production of PGE1 but chronic consumption will lead to depletion of DGLA and PGE1. Withdrawal from alcohol will lead to a precipitous fall in PGE1. PGE1 is known to have profound effects on the nervous system and behaviour. Patients with mania produce more PGE1 than normal while those with depression make less. Alcoholics may drink to maintain a normal PGE1 level, something which will require more and more ethanol as DGLA is depleted. In both animals and humans PGE1 or its precursor, gamma-linolenic acid (GLA) have been shown to attenuate the acute withdrawal syndrome. PGE1 injections prevent the development of fatty liver in alcohol-treated animals. Defective EFA and PGE1 metabolism are known to lead to increased fibrosis, reproductive failure, cardiomyopathy, cardiovascular disorders, gastritis and pancreatitis and could therefore be the basis for these disorders in alcoholics. A PGE1 deficiency could also be responsible for the fetal alcohol syndrome. Three other agents are known to produce constellations of fetal defects very similar to those found in the alcohol syndrome. These other factors are dihphenylhydantoin, lithium, and a deficiency of zinc. These three factors and excessive alcohol consumption all lead to PGE1 deficiency by different routes. If this concept is correct, the key to the management of alcoholism and its medical complications lies in the provision of GLA or DGLA, fatty acids which by-pass the alcohol blocked step and which are unfortunately unlikely to be present in any normal diet. Unlike many concepts of alcoholism and alcohol damage, the EFA/PGE1 idea is very readily testable and already has considerable experimental support.

Topics: 8,11,14-Eicosatrienoic Acid; Alcoholism; Fatty Acids, Essential; Female; Fetal Alcohol Spectrum Disorders; gamma-Linolenic Acid; Humans; Linolenic Acids; Lithium; Liver Cirrhosis, Alcoholic; Pregnancy; Prostaglandins; Prostaglandins E; Substance Withdrawal Syndrome