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

BACKGROUND & AIMS: Muscle wasting in cancer negatively affects physical function and quality of life. This study investigates amino acid metabolism and the association with muscle mass and function in patients with cancer.

METHODS: In 16 patients with advanced cancer undergoing chemotherapy and 16 healthy controls, we administered an intravenous pulse and prime of stable amino acid tracers. We took blood samples to measure the Rate of appearance (Ra), whole body production (WBP), clearance (Cl), and post absorptive whole body net protein breakdown (WBnetPB). Plasma amino acid concentrations and enrichments were analysed by LC-MS/MS. We assessed muscle mass, handgrip/leg/respiratory muscle strength and reported physical activity, quality of life, and physical function.

RESULTS: Muscle strength was lower in cancer patients than in healthy controls. Total and limb muscle mass, reported physical activity and WBnetPB were comparable. WBP and Cl of tau-methylhistidine, leucine, glutamine and taurine were higher in cancer patients as well as glycine Cl. Amino acid metabolism was correlated with low muscle mass, strength, physical function and quality of life.

CONCLUSIONS: Myofibrillar protein breakdown and production of amino acids involved in muscle contractility are up regulated in patients with cancer undergoing chemotherapy and related to muscle weakness and reduced physical outcomes.