linoleic-acid and Alcoholism

Linoleic acid (C18: 2n-6) is a free fatty acid considered as essential in man; this is mainly based on the fact that man is incapable of its synthesis and that its deficiency accounts for a defined clinical picture. Linoleic acid (LA) is an essential component of cellular membranes and plays, therefore, an important role in cells; moreover, it plays a functional part on account of its precursory position of eicosanoids. For these reasons, the skin is a preferential target in case of LA deficiency, which alters the barrier function of the skin as well as the immunoregulation of the epidermic homeostasis. Man's requirement of LA has been estimated 4% of the total energy supply, i.e. 7-10 g daily. Deficiency of LA may arise from various factors: insufficient supply; metabolic anomalies (mostly due to advanced age and hepatopathies which may particularly alter the metabolic process of desaturation). Symptoms due to LA deficiency are xerosis and erythematosquamous dermatitis. The clinical picture being non-specific may be confused with other vitamin deficiencies, all the more because of metabolic interactions between these vitamins and various trace elements. Thus--in order to make the diagnosis--plasmatic fatty acid fractioning by means of gaseous phase chromatography is indicated in case of therapy-resistant eczematous dermatitis associated with malnutrition. These findings may be confirmed by measuring either the ratio of eicosatrienoic acid vs. arachidonic acid or the ratio of LA vs. arachidonic acid (in case of a disturbed metabolism of fatty acids). The treatment consists of regular oral, parenteral or topical application of essential fatty acids. Topical administration is especially indicated, because these patients, although often suffering from impaired intestinal absorption, reveal a tenfold percutaneous absorption rate of fatty acids.

Topics: Aged; Alcoholism; Dermatitis; Humans; Linoleic Acid; Linoleic Acids; Male

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

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

Chow-fed rats were given 15% ethanol in their drinking water for 4 weeks, and then for the next 2 weeks of ethanol exposure they were fed isocaloric semisynthetic diets enriched in either saturated (S) or polyunsaturated (P, linoleic acid) fats. Food intake was lower in ethanol-fed (ETH) than in control (C) rats, but the average body weight gain was similar in ETH and C fed S or P. Intestinal dry weight and the percentage of the intestinal wall comprised of mucosa were more than 2-fold higher in ETH than C fed P, whereas these values were 50% lower in ETH than C fed S. The in vitro jejunal uptake of glucose and galactose was higher in ETH than C fed S, whereas the converse was true when feeding P. These effects were due to differences in the values of the maximal transport rate (Vmax), the Michaelis constant (Km), and the contribution of passive permeation. The relative permeability of the intestine to lipids was unchanged by giving ethanol or by feeding S or P, but the individual rates of uptake of most medium- and long-chain fatty acids and cholesterol were lower in ETH fed P as compared with S. In a second series of studies the acute effect of ethanol exposure was examined: animals were fed S or P for 2 weeks and the intestine was then removed: when 5% ethanol was added directly to the test solutions, there was lower in vitro jejunal and ileal uptake of glucose and higher jejunal uptake of 18:2 when rats were previously fed P, but not in those fed S. In summary; (1) feeding an isocaloric polyunsaturated fatty acid diet has a trophic effect on the intestinal mucosa of animals chronically drinking ethanol; and (2) feeding rats a diet enriched with saturated fatty acids prevents the inhibitory effects of acute and chronic ethanol exposure on the in vitro jejunal uptake of glucose, galactose and lipids observed in animals fed a polyunsaturated diet. Thus, the effect of chronic consumption of ethanol on the active and passive jejunal uptake of nutrients is influenced by the type of lipids in the animal's diet.

Topics: Alcoholism; Animals; Biological Transport, Active; Dietary Fats; Ethanol; Fatty Acids, Nonesterified; Fatty Acids, Unsaturated; Female; Glucose; In Vitro Techniques; Intestinal Absorption; Intestinal Mucosa; Jejunum; Kinetics; Linoleic Acid; Linoleic Acids; Rats; Rats, Inbred Strains

The level of conjugated dienes (CD) in the serum, conjugated linoleic acid isomer in the phospholipid fraction [18:2(9, 11)], and the fatty acid profile in both the serum and in the separated lipid classes were analyzed in current and previous alcohol abusers and in patients with alcoholic liver disease. None of the subjects consumed alcohol for at least 2-3 days prior to blood collection for analysis of lipids. There was no significant difference in CD or in the absolute level of 18:2(9, 11) among the groups, whereas the 18:2(9, 11)/18:2(9, 12) molar ratio was significantly elevated in patients with liver disease. Fatty acid analysis of the whole plasma extract showed that the absolute level of arachidonic acid increased from 4.8 +/- 3.5 mg/dl (n = 9) in lifelong abstainers to 13.4 +/- 4.0 (n = 8) in current ethanol abusers, and its relative level (related to the total fatty acids) from 1.73 +/- 1.34 to 4.55 +/- 1.01 in the same groups. An increased proportion of linoleic acid in the triglyceride and phospholipid fractions from current abusers and patients with liver disease was also found; the percentage of 18:2 in phospholipids increased from 5.4 +/- 5.0 (n = 8) in lifelong abstainers to 14.3 +/- 3.9 (n = 8) in current abusers and 12.7 +/- 2.2 (n = 10) in patients with liver disease. The percentage of 16:0 was significantly lower in the phospholipids of current abusers as compared to lifelong abstainers.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Alcoholism; Arachidonic Acid; Arachidonic Acids; Fatty Acids; Humans; Linoleic Acid; Linoleic Acids; Liver Diseases, Alcoholic; Male; Middle Aged; Phospholipids

The identification of the main dieneconjugated "free-radical marker" in human serum led to a study of free-radical activity in chronic alcoholics. 66 patients were investigated immediately after alcohol withdrawal and over 1-4 weeks' follow-up. The control groups were 76 normal subjects, 78 patients with liver disease, 30 patients on long-term antiepileptic drug treatment, 9 pregnant women, and 99 unselected hospital patients. 82% of chronic alcoholics had a significantly higher than normal level of phospholipid-esterified 9,11 linoleicacid isomer in blood collected within 24 h of their last alcoholic drink. The levels fell to normal over the next 2-4 days but continued to decline within the normal range for 2-3 weeks. There was no rise in the level of the isomer in normal controls after an acute alcohol load. The results suggest that chronic alcoholism may induce a specific detoxifying mechanism which is activated by alcohol and which entails or depends on greatly increased free-radical activity.

Topics: Adolescent; Adult; Aged; Alcoholism; Cholesterol; Chromatography, High Pressure Liquid; Ethanol; Female; Free Radicals; Humans; Isomerism; Linoleic Acid; Linoleic Acids; Male; Middle Aged; Phospholipids; Reference Values; Substance Withdrawal Syndrome; Triglycerides

Topics: Alcoholism; Animals; Free Radicals; Humans; Linoleic Acid; Linoleic Acids; Rodentia

In the body the essential fatty acid (EFA) linoleic acid (18:2, omega-6) is desaturated and chain elongated to form homo-gamma-linoleic acid (20:3, omega-6) and arachidonic acid (20:4, omega-6). Apart from their structural function in cell membranes, the EFAs serve as precursors to the prostaglandins and related substances. The prostaglandins can, in general terms, be described as a defensive regulatory system of importance for cardiovascular, gastrointestinal and urogenital function. Acute intake of ethanol gives facial flushing, inhibition of platelet aggregation and elevation of tissue c-AMP. These effects are consistent with release of vasodilatory and antiaggregating PGs. In epidemiological studies, moderate ethanol intake offers some protection against coronary heart disease. Chronic intake high doses of ethanol is associated with damage to, e.g., liver, heart, brain, immunoregulation and various hormonal systems. Decreased tissue levels of 18:2, 20:4 and PGs have been observed both in animals and man. The conversion of 18:2 to 20:4 is inhibited by chronic ethanol exposure. It is suggested that ethanol depletes the PG precursor pool by a dual mechanism of releasing precursor acids and by inhibiting their synthesis. This would lead to a functional EFA-deficiency, manifested by a hypoactive PG system.

Topics: Alcoholism; Animals; Blood Pressure; Cell Membrane; Eicosanoic Acids; Ethanol; Fatty Acids, Essential; Gastric Mucosa; Humans; Hydroxyprostaglandin Dehydrogenases; Linoleic Acid; Linoleic Acids; Liver; Membrane Fluidity; Membrane Lipids; Platelet Aggregation; Prostaglandin-Endoperoxide Synthases; Prostaglandins

Topics: Adult; Aged; Alcoholism; Humans; Linoleic Acid; Linoleic Acids; Liver Diseases; Male; Middle Aged; Phosphatidylcholines; Triglycerides