EFFECTS OF CACHEXIA DUE TO CANCER ON WHOLE-BODY AND SKELETAL-MUSCLE PROTEIN-TURNOVER

BACKGROUND. Data available in the literature regarding whole body prot ein (WBP) kinetics In patients with cachexia due to cancer are conflic ting. Some authors have reported an increase of WBP synthesis and brea kdown, whereas others have not found any significant changes; only a f ew researchers have investigated more compartments simultaneously. The main purpose of this study was to investigate WBP and skeletal muscle protein (SMP) turnover simultaneously in cachectic patients to unders tand better the mechanisms underlying the general wasting of the host present in cancer cachexia. METHODS. WBP and SMP synthesis and breakdo wn were studied in malnourished patients with advanced gastric carcino ma and in healthy volunteers. Protein turnover was evaluated in a post absorptive slate, using a model based on a primed constant infusion of L-[H-2(5)] phenylalanine and L-[H-2(4)] tyrosine, and by determining the isotopic enrichment and concentration in plasma during a plateau p hase by gas chromatography and mass spectrometry. RESULTS. Rates of WB P synthesis and breakdown did not differ significantly be. between the two groups (whole body synthesis [WBS] of 4.35 +/- 0.2 g/kg/day and w hole body breakdown [WBB] of 4.77 +/- 0.2 g/kg/day in the control grou p and WBS of 3.34 +/- 0.7 g/kg/day and WBB of 4.5 +/- 0.4 g/kg/day in the patient group). The skeletal muscle compartment of the patients sh owed a significantly lower synthesis compared with controls (patients, 9.6 +/- 1.8 nmol/100 mL/minute and control, 25.9 +/- 7.6 nmol/100 mL/ minute; P < 0.05), whereas the breakdown was similar in the two groups . Such reduction in SMP synthesis in the gastric carcinoma patients re sulted in a more negative net balance. CONCLUSIONS. Conflicting data i n the literature may be accounted for by the different selection of pa tients and controls. Furthermore, WBP kinetics is the result of the me tabolism of at least two compartments, the muscle and the nonmuscle co mpartments (including the tumor), which can change in opposite ways. I n patients with cachexia due to cancer, the skeletal compartment appea rs to be the more compromised, with a significant decrease in SMP synt hesis. (C) 1998 American Cancer Society.