Carnitine Mediated Alterations of Ethanol and Fatty Acid Metabolism

The purpose of this dissertation was to examine the effect of dietary carnitine supplementation on ethanol and fatty acid metabolism. Rats were fed Purina chow as such (non-supplemented, NS) or supplemented with 0.5% L-carnitine supplemented CS). Carnitine supplementation for 7d resulted in decreased oxidation of an oral dose of [1-14C]-ethanol. Expired 14CO2 was significantly reduced at hours 4-12 in the CS group. There were no significant differences in urinary excretion of the 14C-label remaining in tissues after 12h was also not significantly affected by carnitine supplementation. Blood-ethanol concentrations (BEC) were 88.5 and 125.9 mg/dl in the NS and CS groups, respectively, 3h post-ethanol administration (PEA). Liver-ethanol concentrations (LEC) were 1.70 and 0.85 μg/mg in the NS and CS groups, respectively 3h PEA. Examination of liver concentrations of pyruvate, lactate, acetoacetate, and 3-hydroxybutyrate revealed no significant differences between the NS and CS groups. Plasma concentrations of lactate were 2-fold higher in the CS group, but pyruvate, acetoacetate and 3-hydroxybutyrate were not significantly different between the two groups. Plasma and liver non-esterified carnitine (NEC), acid soluble acylcarnitine (ASAC) and acid insoluble acylcarnitine (AIAC) concentrations were all significantly higher in the CS group 3h after ethanol administration. The effect of carnitine supplementation on the urinary excretion of ethanol, its metabolites and carnitine was determined by feeding rats the NS and CS diets for 7d. The rats were then given an oral dose of [1-14C]-ethanol and urine was collected for the next twenty-four hours. Food intake, water intake and urine volume were not significantly different between the NS & CS groups over the 24h period. Urinary excretion of ethanol and the 14C-label were not significantly affected by carnitine supplementation. Urinary excretion non-esterified carnitine (NEC), acid-soluble acyl-carnitine (ASAC) and acid-insoluble acyl-carnitine (AIAC) were significantly elevated in the CS group over the 24h period. Supplementary carnitine did not significantly affect the oxidation of [14C(U)]-palmitate. There were no significant differences between the NS and CS groups with regard to the rates of 14CO2 appearance or percent of the dose following 5, 10, 20, 30 & 40 days of feeding CS diet. Ethanol administration resulted in decreased palmitate oxidation, at hours 4-24, but dietary carnitine supplementation did not affect the decreased oxidation due to ethanol