Increased amino acid turnover and myofibrillar protein breakdown in advanced cancer are associated with decreased muscle strength and physical function

Rationale: Weight loss and muscle wasting are common in cancer patients and negatively affect physical function andquality of life. This study investigates the relationship between protein metabolism, muscle strength and physical functionin patients with advanced cancer.Methods: In 16 patients with solid tumours (C) and 16 age- and gender-matched healthy controls (H), we assessedfasted whole body net protein breakdown (netPB), myofibrillar PB (MPB) and rate of appearance (Ra) by pulse IVadministration of stable tracers ([2H3]tau-methylhistidine, 2H3-LEU, 2H2-GLY). We measured net protein synthesis (netPS),and protein digestion (PD: gut function) after intake of a high-protein meal with [1-13C]PHE and 15N-spirulina and primed continuous infusion of [ring-2H5]PHE and [13C9-15N]TYR. We tested FFM-i, handgrip, inspiratory,hand and leg musclestrength, physical activity by PASE and physical function by EORTC-QLQc30 questionnaires. Amino acid concentrations/enrichments by LC-MS/MS, and statistics by unpaired t-tests and spearman correlation tests.Results: FFM-i, handgrip strength and physical activity were similar in C and H, leg and inspiratory muscle strength werelower in C (p<0.05). Fasted netPB (5.9 vs. 6.8 μmol/kg ffm/h), fed netPS (40.2 vs. 43.9 μmol/kg ffm/h) and proteindigestion were not different, MPB and leucine Ra (0.29 vs.0.20 and 114.3 vs. 66.3 μmol/kg ffm/h) and clearance (0.07 vs.0.04 and 1.42 vs. 0.78 L/min) and glycine clearance (1.3 vs. 0.9 L/min) were higher in C (P<0.05). In C Ra-glycine wasassociated with leg extension strength (r=0.51, P=0.06), glycine clearance with impaired physical function (r=-0.59,P=0.04).Conclusion: Patients with advanced cancer with preserved muscle mass and physical activity have an increased aminoacid turnover and myofibrillar protein breakdown, negatively impacting muscle strength and physical function.