8-11-14-eicosatrienoic-acid and Alcoholism

Male reproductive failure and infertility are quite common in alcoholics. There are very high correlations between elevated vasopressin levels and male infertility on the one hand, and probable deficiencies of prostaglandin E1 which may raise levels of PGE2 and endorphins which, in turn, release vasopressin on the other. Since head-out water immersion rapidly decreases vasopressin levels, a suggested joint protocol of head-out water immersion and a prostaglandin E-1 precursor is proposed for male reproductive failure in alcoholics.

Topics: 8,11,14-Eicosatrienoic Acid; Alcoholism; Alprostadil; Humans; Immersion; Infertility, Male; Male; Vasopressins; Water

Plasma phospholipid essential fatty acids and some of their main metabolites, prostaglandins, were measured among habitually violent and impulsive male offenders, who all had alcohol abuse problems, and nonviolent control persons. Linoleic acid (18:2n-6), the precursor of the n-6 fatty acids, was below normal in intermittent explosive disorder, but the dihomogammalinolenic acid (DGLA) (20:3n-6) and some subsequent n-6 acids were at the same time elevated among all offenders. Also, a monounsaturate, oleic acid (18:1n-9) was elevated. The high DGLA correlated with low cholesterol level in intermittent explosive disorder. The arachidonic acid metabolites PGE2 and TxB2 were elevated in violent antisocial personality. The PGE1/DGLA ratio was low in intermittent explosive disorder. The number of registered violent crimes and violent suicidal attempts correlated with high phospholipid DGLA values. The possibility that the high phospholipid DGLA is connected with low free DGLA pool, and therefore low PGE1 formation, among these offenders is discussed.

Topics: 8,11,14-Eicosatrienoic Acid; Adult; Alcoholism; Alprostadil; Cholesterol; Docosahexaenoic Acids; Fatty Acids, Essential; Humans; Impulsive Behavior; Linoleic Acids; Male; Middle Aged; Oleic Acid; Oleic Acids; Prostaglandins; Violence

Aging is characterized by a wide variety of defects, particularly in the cardiovascular and immune systems. Cyclic AMP levels fall, especially in lymphocytes. Delta-6-desaturase (D6D) levels have been found to fall rapidly in the testes and more slowly in the liver in aging rats. D6D is an enzyme which converts cis-linoleic acid to gamma-linolenic acid (GLA). Other factors which inhibit D6D activity are diabetes, alcohol and radiation, all of which may be associated with accelerated aging. In meat eaters or omnivores which can acquire arachidonic acid from food, the main consequences of D6D loss will be deficiencies of GLA, dihomogamma-linolenic acid (DGLA) and prostaglandin (PG) E1. PGE1 activates T lymphocytes, inhibits smooth muscle proliferation and thrombosis, is important in gonadal function and raises cyclic AMP levels in many tissues. It is a good candidate for a key factor lost in aging. Moderate food restriction, the only manoeuvre which consistently slows aging in homoiotherms, raises D6D activity by 300%. Other factors important in regulating D6D and the conversion of GLA to PGE1 are zinc, pyridoxine, ascorbic acid, the pineal hormone, melatonin, and possibly vitamin B3. GLA administration to humans has been found to lower blood pressure and cholesterol, and to cause clinical improvement in patients with Sjogren's syndrome, scleroderma and alcoholism. These diseases are associated with some features of accelerated aging. The proposition that D6D loss is not only a marker of aging but a cause of some of its major manifestations is amenable to experimental test even in humans. The blocked enzyme can be by-passed by giving GLA directly.

Topics: 15-Oxoprostaglandin 13-Reductase; 8,11,14-Eicosatrienoic Acid; Aging; Alcoholism; Alprostadil; Cholesterol; Dietary Fats; Fatty Acid Desaturases; Female; Humans; Linoleoyl-CoA Desaturase; Menopause; Milk, Human; Models, Biological; Pregnancy; Prostaglandins E; Scleroderma, Systemic

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