NUTRITIONAL EFFECTS ON ESSENTIAL FATTY ACID COMPOSITION

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Our studies have demonstrated that alcohol abuse leads to a decrease in the level of long chain polyunsaturated fatty acids like arachidonate (20:4n6) and docosahexaenoate (22:6n3). For example, there is a selective decrease in the level of 22:6n3 in the livers of patients undergoing transplantation subsequent to alcoholic liver disease. It is hypothesized that the lowered level of these important cell membrane constituents leads to alterations in cellular function that may underlie some aspects of alcohol-induced organ injuries and that prevention or restoration of this decrement in essential fatty acids may be of therapeutic benefit to alcoholics. This view was supported by the finding that plasma 22:6n3 was (inversely) correlated with the level of the serotonin metabolite 5-HIAA in the cerebrospinal fluid of early onset alcoholics. Recent studies have focused upon elucidating the ability of humans to biosynthesize these fatty acids in vivo from their 18-carbon precursors as well as the regulation of this pathway. It has been demonstrated for the first time that humans can biosynthesize 20:4n6 in vivo and that this capability has developed by 33 weeks gestational age in infants. The biosynthetic capacity for 20:4n6 and 22:6n3 do not appear to be adequate to supply nervous system requirements during the first week of life. In a related study, it was demonstrated that even very high levels of 18:3n3 could not support the levels of nervous system 22:6n3 observed in well nourished dam-reared rat pups in early development. The largest controlled dietary studies thus far conducted have shown that increased levels of long chain n-3 fatty acids like 20:5n3 and 22:6n3 in the diet lead to a lower accretion of deuterated n-3 metabolites in vivo. These studies support the view that preformed 22:6n3 is essential for proper nervous system development and function and that an important mechanism by which alcohol exerts adverse effects is through the antagonism of this fatty acid.