gamma-linolenic-acid and Substance-Withdrawal-Syndrome

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

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

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

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