Effect of carnitine on muscular glutamate uptake and intramuscular glutathione in malignant diseases

Abnormally low intramuscular glutamate and glutathione (GSH) levels and/or a decreased muscular uptake of glutamate by the skeletal muscle tissue have previously been found in malignant diseases and simian immunodeficiency vi rus (SIV) infection and may contribute to the development of cachexia. We t ested the hypothesis that an impaired mitochondrial energy metabolism may c ompromise the Na+-dependent glutamate transport. A randomized double-blind clinical trial was designed to study the effects of L-carnitine, i.e. an ag ent known to enhance mitochondrial integrity and function, on the glutamate transport and plasma glutamate level of cancer patients. The effect of car nitine on the intramuscular glutamate and GSH levels was examined in comple mentary experiments with tumour-bearing mice. In the mice, L-carnitine trea tment ameliorated indeed the tumour-induced decrease in muscular glutamate and GSH levels and the increase in plasma glutamate levels. The carnitine-t reated group in the randomized clinical study showed also a significant dec rease in the plasma glutamate levels but only a moderate and statistically not significant increase in the relative glutamate uptake in the lower extr emities. Further studies may be warranted to determine the effect of L-carn itine on the intramuscular GSH levels in cancer patients. (C) 2000 Cancer R esearch Campaign.