LOW PLASMA GLUTAMINE IN COMBINATION WITH HIGH GLUTAMATE LEVELS INDICATE RISK FOR LOSS OF BODY CELL MASS IN HEALTHY-INDIVIDUALS - THE EFFECTOF N-ACETYL-CYSTEINE

Skeletal muscle catabolism, low plasma glutamine, and high venous glut amate levels are common among patients with cancer or human immunodefi ciency virus infection. In addition, a high glycolytic activity is com monly found in muscle tissue of cachectic cancer patients, suggesting insufficient mitochondrial energy metabolism. We therefore investigate d (a) whether an ''anaerobic physical exercise'' program causes simila r changes in plasma amino acid levels, and (b) whether low plasma glut amine or high glutamate levels are risk factors for loss of body cell mass (BCM) in healthy human subjects, i.e., in the absence of a tumor or virus infection. Longitudinal measurements from healthy subjects ov er longer periods suggest that the age-related loss of BCM occur mainl y during episodes with high venous glutamate levels, indicative of dec reased muscular transport activity for glutamate. A significant increa se in venous glutamate levels from 25 to about 40 mu M was seen after a program of ''anaerobic physical exercise.'' This was associated with changes in T lymphocyte numbers. Under these conditions persons with low baseline levels of plasma glutamine, arginine, and cystine levels also showed a loss of BCM. This loss of BCM was correlated not only wi th the amino acid levels at baseline examination, but also with an inc rease in plasma glutamine, arginine, and cystine levels during the obs ervation period, suggesting that a loss of BCM in healthy individuals terminates itself by adjusting these amino acids to higher levels that stabilize BCM. To test a possible regulatory role of cysteine in this context we determined the effect of N-acetyl-cysteine on BCM in a gro up of subjects with relatively low glutamine levels. The placebo group of this study showed a loss of BCM and an increase in body fat, sugge sting that body protein had been converted into other forms of chemica l energy. The decrease in mean BCM/body fat ratios was prevented by N- acetyl-cysteine, indicating that cysteine indeed plays a regulatory ro le in the physiological control of BCM.