Amino acid metabolism and inflammatory burden in ovarian cancer patients undergoing intense oncological therapy.
OBJECTIVE
Cancer and oncological therapy are associated with a progressive physical deterioration, malnutrition, and enhanced inflammatory burden. Our considerable data showing the strong anabolic potential of amino acids (AA) led us to test whether AA can acutely stimulate muscle protein synthesis in cancer patients (CA) undergoing intense chemotherapy.


METHODS
Mixed muscle fractional synthesis rate (FSR), rates of phenylalanine appearance and disappearance (Ra and Rd), and net phenylalanine balance (NB) were measured during a primed constant infusion of L-[ring-(2)H(5)]phenylalanine. Blood and muscle tissue samples were collected in the basal state and following ingestion of 40 g of AA given in 30 mL boluses every 10 min for 3h. Serum and tissue cytokines and NF-kappaB expression in skeletal muscle were measured and compared to normative, healthy older controls (OC).


RESULTS
Skeletal muscle TNF-alpha, IL-6, and NF-kappaB were elevated in CA. FSR and model-derived protein synthesis (Rd) increased significantly from basal to AA (FSR: 0.052+/-0.009 vs. 0.120+/-0.008%h(-1), P<0.001; Rd: 23.1+/-4.1 vs. 36.4+/-5.0 nmol min(-1) 100 mL leg(-1), P0.05). Model-derived protein breakdown (Ra) remained unchanged from basal to AA. Phenylalanine NB improved from a negative basal value (-16+/-2) to zero (0.8+/-6 nmol min(-1) 100 ml leg(-1), P0.05) following AA.


CONCLUSIONS
Despite advanced cancer, ongoing therapy, and an enhanced inflammatory burden, AA were capable of acutely stimulating muscle protein synthesis in these patients.
Dillon
E L
EL
Department of Internal Medicine, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555-1060, USA.
Volpi
Elena
E
Wolfe
Robert R
RR
Sinha
Sandeep
S
Sanford
Arthur P
AP
Arrastia
Concepcion D
CD
Urban
Randall J
RJ
Casperson
Shanon L
SL
Paddon-Jones
Douglas
D
Sheffield-Moore
Melinda
M
D000596:Amino Acids / Q000378:metabolism; D001774:Blood Chemical Analysis; D016207:Cytokines / Q000378:metabolism*; D003903:Deuterium; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000503:physiopathology; D008875:Middle Aged; D009124:Muscle Proteins / Q000096:biosynthesis*; D016328:NF-kappa B / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000503:physiopathology; D010649:Phenylalanine / Q000493:pharmacokinetics*