Ketogenic effects of carnitine in patients with muscular dystrophy and cytochrome oxidase deficiency.

The effects of a single oral dose of carnitine on fasting-induced ketosis was investigated in four normal individuals, five patients with muscular dystrophy, and one patient with a generalized cytochrome c oxidase deficiency. Plasma carnitine, free fatty acids, glucose, insulin, and glucagon were also measured. Normal individuals showed an average 0.09 mM increase in blood beta-hydroxybutyrate concentration during a 12- to 18-hr period of fasting and carnitine administration did not affect this response (average: 0.12 mM). Muscular dystrophy patients showed a greater fasting-induced elevation in beta-hydroxybutyrate (average 0.29 mM) and carnitine administration greatly enhanced this ketogenic response (average 0.84 mM). The cytochrome c oxidase deficient patient showed an even larger increase in beta-hydroxybutyrate with fasting (1.67 mM) and carnitine further augmented this ketotic effect (3.78 mM). Plasma free fatty acids were also elevated in patients that showed enhanced ketosis. Plasma glucagon concentration did not change, but insulin levels decreased during the 12- to 18-hr period of fasting; no major differences were found between controls and patients. These results indicate that some patients with muscular dystrophy and cytochrome c oxidase deficiency are more prone to develop ketosis than normal individuals and that carnitine administration enhances this response. Since both muscular dystrophy patients and the patient with cytochrome c oxidase deficiency had similar ketogenic responses, the data suggest that ketone body utilization may be impaired in these patients. The ability of L-carnitine to be ketogenic should be considered in the treatment of these patients.