Relationship of free fatty acids and magnesium in ethanol withdrawal in dogs

A group of dogs was conditioned to drink 4-6 g ethanol/kg/day for long periods. Ethanol ingestion was interrupted at monthly intervals in order to study some metabolic changes of the withdrawal period. Plasma long chain free fatty acids (FFA) increased by a maximum mean of 1.4 meq/liter (threefold), and magnesium (Mg) decreased by a maximum mean of 0.4 meq/liter (75% of control during the first 24 hr of simple ethanol withdrawal. Because magnesium salts of FFA are very insoluble, these divergent changes of Mg and FFA suggest that lipolysis may be responsible for the hypomagnesemia that occurs in ethanol withdrawal. In order to control lipolysis, glucose-insulin, glucose alone, and fructose alone were given intravenously for a 4-hr period beginning 14 hr after withdrawal. FFA fell by a maximum of 65% or 0.44 meq/liter and Mg fell by a maximum of 0.31 meq/liter during the glucose-insulin infusions. Nicotinic acid (10-20 mg/kg) in saline produced an identical drop in FFA and a slight rise in Mg. After stopping the nicotinic acid infusion, a sharp rebound rise in FFA and a sharp fall in Mg occurred similar to the simple withdrawal experiments. The sharp divergent changes in FFA and Mg after cessation of nicotinic acid infusion support the prime role of FFA-effecting movements of Mg and the thesis that FFA bind Mg. Control of lipolysis is theoretically sound in therapy of the ethanol withdrawal syndrome.